Virulence Factors and Antifungal Susceptibility Patterns in Vulvovaginal Candidiasis Isolates

Authors

Keywords:

vaginal candidiasis, Candida albicans, enzymatic activity, antifungal susceptibility.

Abstract

Introduction: Vulvovaginal candidiasis is a common reason for medical consultation, and the number of patients experiencing recurrent symptoms is increasing. Although Candida albicans is its main etiological agent, recent studies have shown a rise in the incidence of other species. Virulence traits contributing to the clinical presentation include dimorphism, adherence, biofilm formation, and secretion of lytic enzymes

Objectives: To determine the production of virulence factors (phospholipases, proteases) and the in vitro antifungal susceptibility to nystatin and fluconazole of Candida spp. isolates from cases of vulvovaginal candidiasis.

Methods: Sixty isolates belonging to the genus Candida, from patients with vulvovaginal candidiasis, were studied. The production of phospholipases and proteases was evaluated using specific media for their detection, and the Pz indices referring to the production ability of each isolate were quantified. The antifungal susceptibility study followed the guidelines established in document M27-A3 from the CLSI.

Results: Out of the 60 isolates, 33 showed phospholipase activity (55%) and 34 were protease producers, accounting for 56.67%. Significant differences were found in phospholipase production between C. albicans and non-albicans Candida, but not in protease production. Only one C. albicans isolate was resistant to nystatin. For fluconazole, resistance was observed in ten C. albicans isolates, one C. glabrata, and one C. famata. These isolates reached a minimum inhibitory concentration of ≥ 64 µg/mL for this antifungal.

Conclusions: These results provide a more comprehensive understanding of the etiology of vulvovaginal candidiasis, which is of great epidemiological and therapeutic value.

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Author Biography

Mayda Rosa Perurena Lancha, Instituto de Medicina Tropical ¨Pedro Kourí (IPK), La Habana

Laboratorio de Micología del Departamento Bacteriología-Micología del IPK

References

Talapko J, Juzbašić M, Matijević T, Pustijanac E, Bekić S, Kotris I, et al. Candida albicans-the virulence factors and clinical manifestations of infection. J. Fungi. 2021;7:79. DOI: https://doi.org/10.3390/jof7020079

Ge G, Yang Z, Li D, Zhang N, Chen B, Shi D. Distinct host immune responses in recurrent vulvovaginal candidiasis and vulvovaginal candidiasis. Front Immunol. 2022;13:959740. DOI: https://doi.org/10.3389/fimmu.2022.959740

Sobel JD. Recurrent vulvovaginal candidiasis. Am J of Obst Gynecol. 2016;214:15-21. DOI: https://doi.org/10.1016/j.ajog.2015.06.067.

Lopes JP, Lionakis MS. Pathogenesis and virulence of Candida albicans. Virulence. 2022;13:89-121. DOI: https://doi.org/10.1080/21505594.2021.2019950

Czechowicz P, Nowicka J, Gościniak G. Virulence factors of Candida spp. and host immune response important in the pathogenesis of vulvovaginal candidiasis. Int J Mol Sci. 2022;23(11):5895. DOI: https://doi.org/10.3390/ijms23115895

Arechavala A, Negroni R, Santiso G, Depardo R, Bonvehí P. Chronic recurrent vulvovaginitis is not only due to Candida. Rev Iberoam Micol. 2021:38(3):132-37. DOI: https://doi.org/10.1016/j.riam.2021.03.002

Aslani N, Kokabi R, Moradi F, Abbasi K, Vaseghi N, Hosein M. Characterization of Candida species isolated from vulvovaginal candidiasis by MALDI-TOF with in vitro antifungal susceptibility profiles. Curr Med Mycol. 2021;7(4):6-11. DOI: https://doi.org/10.18502%2Fcmm.7.4.8405

Miró MS, Rodríguez E, Vigezzi C, Icely PA, Gonzaga de Freitas M, Riera FO, et al. Candidiasis vulvovaginal: una antigua enfermedad con nuevos desafíos. Rev Iberoam Micol. 2017;34(2):65-71. DOI: https://doi.org/10.1016/j.riam.2016.11.006

Fan S, Liu X, Wu C, Xu L, Li J. Vaginal nystatin versus oral fluconazole for the treatment for recurrent vulvovaginal candidiasis. Mycopathologia. 2015;179:95-101. DOI: https://doi.org/10.1007/s11046-014-9827-4

Kombade SP, Abhishek KS, Mittal P, Sharma C, Singh P, Nag VL. Antifungal profile of vulvovaginal candidiasis in sexually active females from a tertiary care hospital of Western Rajasthan. J Family Med Prim Care. 2021;10:398-402. DOI: https://doi.org/10.4103%2Fjfmpc.jfmpc_1124_20

Marcos-Arias C, Eraso E, Madariaga L, Aguirre JM, Quindós G. Phospholipase and proteinase activities of Candida isolates from denture wearers. Mycoses. 2009;54:6-10. DOI: https://doi.org/10.1111/j.14390507.2009.01812.x

Ge YP, Lu GX, Shen YN, Liu WD. In vitro evaluation of phospholipase, proteinase, and esterase activities of Candida parapsilosis and Candida metapsilosis. Mycopathologia. 2011;172:429-38. DOI: https://doi.org/10.1007/s11046-011-9440-8.Epub 2011 Jun 23.

Clinical and Laboratory Standards Institute. M27-A3. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts: third edition. Wayne, PA: CLSI;2008.

Clinical and Laboratory Standards Institute. M59. Epidemiological Cutoff Values for Antifungal Susceptibility Testing second edition. Wayne, PA:CLSI;2018.

Kuriyama T, Williams DW, Bagg J, Coulter WA, Ready D, Lewis MA. In vitro susceptibility of oral Candida to seven antifungal agents. Oral Microbiology and Immunology. 2005;20(6):349-53. DOI: https://doi.org/10.1111/j.1399-302x.2005.00236.x

Editorial, E. Declaración de Helsinki de la Asociación Médica Mundial. Arbor. 2008 [01/10/2022];184(730):349-52. Disponible en: https://arbor.revistas.csic.es/index.php/arbor/article/view/183

Balakrishnan SN, Yamang H, Lorenz MC, Chew SY, Lung LT. Role of vaginal mucosa, host immunity and microbiota in vulvovaginal candidiasis. Pathogens. 2022 Jun;11(6):618. DOI: https://doi.org/10.3390/pathogens11060618

Kalaiarasan K, Singh R, Chaturvedula L. Changing virulence factors among vaginal non albicans Candida species. Indian Journal of Medical Microbiology. 2018;36:3. DOI: https://doi.org/10.4103/ijmm.IJMM_18_94

Gorgui DL. Caracterización fenotípica de aislamientos provenientes de pacientes con candidiasis vulvovaginal [Trabajo de Terminación de Residencia]. La Habana: Instituto Medicina Tropical Pedro Kourí (IPK);2013.

Hacioglu M, Bozkurt CG, Savage PB, Seher AB. Antifungal susceptibilities, in vitro production of virulence factors and activities of ceragenins against Candida spp. isolated from vulvovaginal candidiasis. Medical Mycology. 2019;57:291-99. DOI: https://doi.org/10.1093/mmy/myy023

Bezerra E, De Paula R, Amante P, Dos Santos R. Enzymatic and hemolytic activity in different Candida species. Rev Iberoam Micol. 2015;32:79-82. DOI: https://doi.org/10.1016/j.riam.2013.11.003

Ramos L, Barbedo LS, Braga-Silva LA, dos Santos AL, Pinto MR, Sgarbi DB. Protease and phospholipase activities of Candida spp. isolated from cutaneous candidiasis. Rev Iberoam Micol. 2015;32(2):122-5. DOI: https://doi.org/10.1016/j.riam.2014.01.003

Kantarcioglu A, Yücel SA. Phospholipase and protease activities in clinical Candida isolates with reference to the sources of strains. Mycoses. 2002;45:160-5. DOI: https://doi.org/10.1046/j.1439-0507.2002.00727.x.

Mayer FL, Wilson D, Hube B. Candida albicans pathogenicity mechanisms. Virulence. 2013;4(2):119-28. DOI: https://doi.org/10.4161/viru.22913.

Silva S, Negri M, Henriques M, Oliveira R, Williams DW, Azeredo J. Adherence and biofilm formation of non-Candida albicans Candida species. Trends Microbiol. 2011;19(5):241-47. DOI: https://doi.org/10.1016/j.tim.2011.02.003.

Llovera V, Fernández CM. Susceptibilidad in vitro de aislamientos vaginales de Candida frente a clotrimazol y nistatina. Rev Cubana Med Trop. 2003 [01/10/2022];55(3):138-45. Disponible en: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S0375-07602003000300002

Prieto LM, Díaz LA, Illnait MT, Perurena MR, Cantelar N, Fernández CM. Susceptibilidad a la nistatina de aislamientos bucales de Candida y su correlación con la respuesta al tratamiento. Rev Cubana Med Trop. 2010 [01/10/2022];62(3):237-44. Disponible en: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid= S0375-07602010000300012

Diaz MC, Camponovo R, Araya I, Cerda A, Santander MP, Carrillo AJ. Identificación y sensibilidad antifúngica in vitro de Candida spp. de origen vaginal a fluconazol, clotrimazol y nistatina. Rev Esp Quimioter. 2016 [01/10/2022];29(3):151-54. Disponible en: https://repositorio.uchile.cl/handle/2250/160183

Carolus H, Pierson S, Lagrou K, Van Dijck P. Amphotericin B and other polyenes—discovery, clinical use, mode of action and drug resistance. J Fungi. 2020;6(321):1-21. DOI: https://doi.org/10.3390/jof6040321

Perurena MR, Pérez Y, Fernández CM, Mertínez G, Illnait MT. Susceptibilidad antifúngica de aislados vaginales de Candida spp. Rev Cubana Med Trop. 2016 [01/10/2022];68(3). Disponible en: https://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S0375-07602016000300007

Espinel A, Pfaller M, Bustamante B, Canton E, Fothergill A, Fuller J, et al. Multilaboratory study of epidemiological cutoff values for detection of resistance in eight Candida species to fluconazole, posaconazole and voriconazole. American Society for Microbiology. 2014;58:2006-12. DOI: https://doi.org/10.1128/AAC.02615-13.

Singh A, Singh P, Groot T, Kumar A, Mathur P, Tarai B, et al. Emergence of clonal fluconazole – resistant Candida parapsilopsis clinical isolates in a multicentre laboratory – based surveillance study in India. J Antimicrob Chemother. 2019;74:1260-68. DOI: https://doi.org/10.1093/jac/dkz029

Donders GG, Grinceviciene S, Ruban K, Bellen G. Vaginal pH and microbiota during fluconazole maintenance treatment for recurrent vulvovaginal candidosis (RVVC). Diagn Microbiol Infect Dis. 2020;97(2):115024. DOI: https://doi.org/10.1016/j.diagmicrobio.2020.115024

Adjapong G, Hale M, Garrill A. An investigation of the distribution of Candida species in genitourinary candidiasis and pelvic inflammatory disease from three locations in Ghana. African Journal of Microbiology Research. 2014;8(6):470-75. DOI: https://doi.org/10.5897AJMR2013.6407

Arechavala A, Bianchi I, Robles MH, Santiso AM, Negroni R. Identificación y sensibilidad frente a fluconazol y albaconazol de 100 cepas de levaduras aisladas de flujo vaginal. Rev Iberoam Micol. 2007;24:305-08. DPI: DOI: https://doi.org/10.1016/S1130-1406(07)70061-X

Hong N, Lei Y, Chen H, Chen X, Ming K, Hu D. Genotyping and drug resistance profile of clinical isolates of Candida albicans from vulvovaginal candidiasis in the Eastern China. Mycopathologia. 2022 [01/10/2022];187(2-3):217-24. Disponible en: https://rdcu.be/dbiiu

Sobel JD, Sobel R. Current treatment options for vulvovaginal candidiasis caused by azole-resistant Candida species. Expert Opin Pharmacother. 2018;19(9):971-7. DOI: https://doi.org/10.1080/14656566.2018.1476490

Sanguinetti M, Posteraro B, Lass-Florl C. Antifungal drug resistance among Candida species: mechanisms and clinical impact. Mycoses. 2015;58(S2):2-13. DOI: https://doi.org/10.1111/myc.12330

Jallow S, Govender NP. Ibrexafungerp: A first in class oral triterpenoid glucan synthase inhibitor. J. Fungi. 2021;7:163-82. DOI: https://doi.org/10.3390/jof7030163

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Published

2024-08-16

How to Cite

1.
Perurena Lancha MR, Caballero Rivero B, Velar Martínez RE, San Juan Galán J, Martínez Machín G, Fernández Andreu CM, et al. Virulence Factors and Antifungal Susceptibility Patterns in Vulvovaginal Candidiasis Isolates. Rev Cuba Med Tropical [Internet]. 2024 Aug. 16 [cited 2025 Feb. 21];76. Available from: https://revmedtropical.sld.cu/index.php/medtropical/article/view/979

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